This Cancer Center Support Grant application from the University of Pittsburgh Cancer Institute, an NCI-designated Comprehensive Cancer Center, seeks support for years 23-27. The UPCI is organized as a matrix center that integrates cancer research, clinical care, and cancer outreach across the University of Pittsburgh and its affiliated health system, UPMC. The UPCI includes 348 members from 37 academic departments who have come together to work to reduce the burden of cancer through cancer-related basic, translational, clinical, behavioral, epidemiological, prevention and control research. Total annual extramural cancer research funding (direct costs) to UPCI was $109.5 million (peer-reviewed $95M, non-peer-reviewed $14.5M) on October 1, 2009 of which $42.5M was received from the National Cancer Institute. The commitment of UPCI to transdisciplinary cancer research is exemplified by the fact that its members lead three SPORE grants (lung, head and neck, and skin cancers), eight cancer-focused POIs, two Early Detection Research Network grants, and a phase I UOl. The impact of the cancer research driven by UPCI and its members can be seen in the more than 4,400 unique publications by UPCI investigators from 2004-2009 of which 45% represent collaborative efforts (17% intra-programmatic, 20% inter-programmatic, and 8% both). The integration of investigators at the main University of Pittsburgh campus with clinicians from a unique clinical care network encompassing about 40 UPMC community cancer centers across Western Pennsylvania has enabled enhanced patient access to clinical trials throughout our catchment area in a highly productive way. In 2008 a total of 11,484 patients were entered in the cancer registry. During that same year 1,158 and 2,508 patients entered interventional and non-interventional clinical trials, respectively. It is noteworthy that in 2008 30% of accruals to interventional trials were to investigator-initiated trials and 40% of accruals to interventional tials took place at UPMC community cancer centers. This renewal application requests support for twelve scientific research Programs, fifteen Shared Facilities, Protocol-Specific Research Support, Protocol Review and Monitoring System, planning and evaluation activities, developmental funds, senior leadership, staff investigators, and administration.